Efficacy and safety of human-derived neural stem cell in patients with ischaemic stroke: study protocol for a randomised controlled trial.

INTRODUCTION: Stroke is the most common cause of neurological disability in adults worldwide. Neural stem cell (NSC) transplantation has shown promising results as a treatment for stroke in animal experiments. The pilot investigation of stem cells in stroke phase 1 and phase 2 trials showed that transplantation of the highest dose (20 million cells) was well tolerated. Preliminary clinical benefits have also been observed. However, the trials were open-label and had a small sample size. Furthermore, human NSCs (hNSCs) were intracerebrally implanted, and some serious adverse events were considered to be related to the surgical procedure. Therefore, we plan to conduct a double-blinded, randomised controlled trial to test the safety and efficacy of intranasal injection of hNSCs. METHODS AND ANALYSIS: This single-centre, randomised, double-blinded, parallel-controlled trial will be conducted in China. Sixty patients with ischaemic stroke who met the qualification criteria will be randomly divided into two groups: the NSCs and control groups. All participants will receive intranasal administration of hNSCs or placebo for 4 consecutive weeks. Patients will be followed up at baseline and at 4, 12, 24 and 48 weeks after intervention. The primary outcome is the National Institutes of Health Stroke Scale score (4, 12, 24 weeks after intervention). Secondary outcomes include the modified Rankin scale, Barthel index, Mini-Mental State Examination score (4, 12, 24 weeks after intervention) and cranial MRI changes (24 and 48 weeks after intervention). All adverse events will be recorded during the study period. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of Ren Ji Hospital (2018-009). All subjects will provide informed consent. The results will be accessible in peer-reviewed publications and will be presented at academic conferences. TRIAL REGISTRATION: ChiCTR1900022741; Chinese Clinical Trial Registry.